the film version of And the Band Played On, a book about
the origins of the AIDS epidemic, written by Randy Shilts,
Matthew Modine played the role of a hotshot
disease investigator at the Centers for Disease Control (CDC).
Modine's character was Don Francis, who would later start the company now known as VaxGen Inc. - one of the first commercial ventures to take on the human immunodeficiency virus, which causes AIDS.
I talked with Francis at some length in early 1996, the formative stage of his odyssey to find a vaccine against AIDS. Even then, he was incensed by what he considered to be pointless naysaying.
"Where's the urgency?" he demanded to know. "If you have a fire raging out of control, do you load the fire trucks with water and then sit around and polish them?"
These days, the pursuit of the AIDS vaccine is gaining momentum, even if the urgency is less than might be desired considering the scope of the AIDS disaster. Now, however, it is up to Lance Gordon, a University of Connecticut-trained immunologist, world-class vaccine inventor and current CEO of VaxGen, to prove that the formula to quell the AIDS epidemic soon may be at hand.
VaxGen was spun off from the biotech pioneer Genentech in 1995 to focus on innovative strategies for preventing infectious disease, including the development of an AIDS vaccine. One of Gordon's responsibilities is analyzing the key findings from the first large-scale human trial of a vaccine against HIV, called AIDSVAX, among gay men in North America, Puerto Rico and
the Netherlands. The trial tested the effectiveness of a synthetic copy of an AIDS-virus protein known as gp120. There is also a companion study in Thailand that will be ready for analysis later this year.
When Gordon announced his initial findings in February, the results of the AIDSVAX trials did not provide the definitive results hoped for, but produced some intriguing hints for protections against HIV in the black and non-Hispanic minority volunteers who received the vaccine.
"The results are fascinating and surprising," Francis, who is now president of VaxGen, says. "We think they're scientifically and socially important. It's at least a beginning."
These AIDS-virus trials mark a turning point in the AIDS epidemic. Anti-viral regimens have turned the invariably fatal disease into a more chronic, treatable condition. But some 40,000 new HIV infections happen every year, according to CDC reports. It's up to Gordon and other vaccine pioneers to bring that number down.
Gordon made the rounds late last year at the UConn Health Center, where he spoke with several faculty members in the School of Medicine about potential collaborations and clinical investigations. Besides spearheading the push for the first AIDS vaccine, Gordon also is charged with broadening his company's portfolio, lately winning government contracts to develop a new vaccine against anthrax and planning for other bioterror-related projects.
"He's incredibly sharp," says infectious disease specialist Stephen Wikel, who works on mosquito-borne diseases as part of the UConn Center for Microbial Pathenogenesis. "It's pretty obvious that he's a good businessman and certainly a competent scientist."
Gordon is prominent in vaccine circles for developing the first conjugate vaccine, a technology that links proteins and bacterial components to produce the desired immune response for protection against a disease. The first such vaccine proved successful against the microbe that causes meningitis in children.
Gordon, whose resumé includes CEO stints at Oravax and North American Vaccines, moves into the AIDS vaccine spotlight with the same ears-wide-open attentiveness and careful focus to detail that seem to have marked his entire career. He was a Ph.D. student at UConn in the mid-1970s, where he earned his doctorate in immunology in 1978. His advisor, Irving Goldschneider, was one of three people who invented the first vaccine against adult meningitis, a devastating bacterial infection of the central nervous system.
"I knew about the work that was going on," Gordon says, adding that discussions with Goldschneider helped stimulate what became a lifelong interest in vaccines.
At VaxGen headquarters in Brisbane, Calif., just south of San Francisco, a typically balmy winter day passes these days with little time to spare. There are scientists to consult, regulators to cajole, investors to reassure.
Yet Gordon still found a bit of time to reminisce. In fact, he seemed to welcome the opportunity to look back, a respite during a period when all the pressure is on him to look forward.
His career interest in battling disease has a personal dimension. As a child, he was afflicted by polio, sustaining a 20 percent loss in muscle mass and still earning varsity in track during high school. Early in his corporate career, while working at Connaught Laboratories in Pennsylvania, he scored his first big success, designing the first conjugate vaccine against the widely feared Haemophilus influenzae b, known as Hib. Such vaccines resulted in a 99.1 percent reduction in a systemic disease that once caused most of the acquired mental retardation cases in the United States and killed 5 to 10 percent of infected infants.
Despite such past successes, Gordon made no predictions about the ongoing battle against HIV. In a lengthy interview and several e-mail exchanges just before the AIDSVAX trial results were released, Gordon simply pointed to the evidence at hand, mostly from primate studies and small-scale human testing. The data suggest that gp120 in VaxGen's formulation can be reliably counted on to create neutralizing antibodies in those who take the injection, a trait known as "immunogenicity." How that may translate in the real world is anyone's guess - and Gordon is not one to guess whether any HIV vaccine will ultimately work.
"I can tell you the rationale is very solid," he says. "The product is highly immunogenic in everyone who's received it. It's been very stable throughout 30,000 doses, and there's been no significant product-related adverse events. It showed 100 percent protection in the chimpanzee models of the disease, which are the best models and really the only model for human disease."
Gordon realizes better than anyone that the odds are against anything approaching 100 percent effectiveness. Few experts, in fact, expect any first vaccine will prove potent enough to stop AIDS dead in its tracks. The important point is that AIDSVAX is the only product so far to have made it into advanced clinical trials. Even before the findings were made public, plans were being laid for further studies and testing of AIDSVAX in perhaps more effective combinations, including a plan to try it in conjunction with a much different anti-HIV strategy known as a "prime-boost" vaccine.
"There are many different strategies," Gordon says. "Many different companies and organizations over the years have had many different ways of taking on the challenge."
He jabbed a finger into the tabletop to emphasize the point: "This is the only one," he says. "The only product in advanced trials on HIV so far. There is a lot going on in terms of preclinical investigation. But this is the only one in field trials."
Creating an AIDS vaccine is nothing if not a passion at VaxGen, starting with Don Francis and his railing about official inaction in the early going, now embodied in Gordon's quieter determination to unlock the mystery.
It's extraordinarily complicated: One must first work out all the molecular details, then prove the safety of the formulation, then show that it can be manufactured. Then the real challenge: showing an unproven vaccine contender can be tested safely in the field without engendering risk-taking behavior, which of course would increase the infection rate in the very population the vaccine is aimed at protecting.
The idea behind gp120 is deceptively simple: Show the body the nontoxic "flag" from the surface of the AIDS virus so that the immune system will know what to do when the real viral invaders come along. The problem is that the HIV invaders can change flags: One of the hallmarks of the AIDS virus is its ability to rapidly mutate. Beat it down in one form and it bounces right back in another.
Moreover, even if the original AIDSVAX or subsequent versions prove capable of quelling the HIV infection rate, there are also economic factors to consider: Will those who need it - including people in the poor nations of sub-Saharan Africa, regions of the former Soviet Union and an expanding list of Asian countries - be able to afford it? How much profit will likely be in it for the company that Gordon must make profitable?
Better than just about anyone, Gordon knows the perverse economics of preventive medicine: For 2002, VaxGen reported a net loss of $31.7 million.
"Vaccines have traditionally been viewed as the poor step-child of the pharmaceutical industry," he says, noting that many don't view vaccines as a part of the industry at all. The global vaccine market is worth about $6 billion in sales per year, including all products, from all manufacturers, in all countries. Some individual drugs command more than that. Moreover, once a vaccine is truly effective, people tend to stop worrying about the disease - and cease being willing to pay big money for a vaccine against what comes to be perceived as a nonexistent threat. That's why many old-line vaccine makers have dropped out of the business in recent years. Companies that are left must wrestle with manufacturing difficulties, escalating liability costs, regulatory hassles and price controls.
Meanwhile, Gordon is trying to make sure his company's fate does not rest solely on any single product. In December, for example, VaxGen announced an agreement with a Japanese company that will allow VaxGen to initiate development of a smallpox vaccine that has been used in Japan for over 20 years with a frequency of reaction much lower than the vaccine currently being used in the United States. VaxGen is awaiting U.S. Food and Drug Administration approval to proceed with clinical trials.
VaxGen also has been awarded a contract from the National Institute of Allergy and Infectious Diseases to develop a new anthrax vaccine and to create a feasibility plan to manufacture an emergency stockpile of 25 million doses.
Gordon vows the work with AIDSVAX will go on until the FDA approves it as being effective against HIV infection. "We intend to continue development of this vaccine through licensure, including additional studies as necessary, for use in groups in which the vaccine demonstrated a significant reduction in infection," he says. "We also will continue our work on the vaccine to make it more broadly effective."
All of this does not leave much time for relaxing with his hobbies. "I enjoy spending time with my family, and woodworking and restoring classic cars are my hobbies, but vaccines are my passion," he says. "I really enjoy it and get enormous satisfaction from working in this field. Vaccines have been incredibly effective in eliminating some of history's greatest scourges. There's no other field where I can imagine having more impact on the quality and quantity of life."
UConn leading the way in smallpox immunization
Robert Fuller, M.D., director, Department of Emergency Medicine at the UConn Health Center, receives the smallpox vaccination from Marcia Trapé, Clinical Director for Employee Health. Staff from the UConn Health Center and the Connecticut Department
of Public Health received the first smallpox vaccinations as part of the nationwide
program to protect health care workers.
Fuller says the program was scheduled to reach every hospital in Connecticut by the end of March in order to vaccinate teams of health care workers statewide. Additionally, each week a clinic at the UConn Health Center provides vaccinations for independent health care providers.
Making marks in vaccine research at UConn
UConn scientists are pioneering new fields of
discovery to find ways to fight diseases in humans and animals through innovative vaccine research.
Pramod Srivastava at the Center for Immunotherapy of Cancer and Infectious Diseases in the UConn Health Center is pioneering a new approach in the fight against cancer and infectious diseases.
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| Pramod Srivastava |
Believing that each tumor is unique, Srivastava has developed individualized vaccines of purified heat shock proteins taken from each patient's tumor. This vaccine alerts the body's immune system to attack the invading cancer without harming healthy cells, unlike more traditional cancer therapies such as chemotherapy and radiation.
This trailblazing theory of fighting cancers is showing great promise. Clinical trials for a vaccine for breast cancer and kidney cancers and leukemia and melanoma are currently underway at the UConn Health Center.
In UConn's Center of Excellence for Vaccine Research, projects are underway to develop novel vaccines that will prevent diseases in food animals such as cows, chickens and pigs.
"Despite advances in veterinary medicine and animal husbandry, pathogenic microbes are now, and will continue to be, the most significant cause of animal disease and economic loss to the U.S. food animal agricultural community," says Steven J. Garey, director of the center.
In collaboration with the U.S. Department of Agriculture's Plum Island, N.Y., research laboratory, Garey says UConn researchers are developing vaccines to fight respiratory disease in cows, pigs and chickens. They have a patent pending on a vaccine, researched and developed in UConn labs, to prevent respiratory disease in chickens.
At the Center for Microbial Pathogenesis at the UConn Health Center, a research team led by Stephen Wikel is focusing on how to prevent the spread of disease from the bites of ticks and mosquitoes. Insect bites not only cause inflammation in animals and humans but also are how diseases are transmitted.
"What we're focusing on is the identification of saliva in ticks and mosquitoes that can be used to induce an immune response to block feeding," Wikel explains. "If you immunize dogs and humans, you're protecting target hosts and can prevent them from getting infected."
They are using this knowledge to develop a vaccine to target molecules introduced by the tick that are essential for feeding and transmission of disease.